Deckard-Janatpour K, Kragel S, Teplitz R L, Min B H, Gumerlock P H, Frey C F, Ruebner B H
Department of Pathology, University of California Davis Medical Center, Sacramento 95817, USA.
Arch Pathol Lab Med. 1998 Mar;122(3):266-72.
Tumors of the pancreas with osteoclast-like giant cells are of uncertain histogenesis and aggressiveness. Their relationship, if any, to undifferentiated (anaplastic) carcinomas of the pancreas with pleomorphic giant cells is also not clear.
Eleven tumors with osteoclast-like giant cells were studied by immunohistochemistry for epithelial and mesenchymal markers, as well as for a proliferation marker (Ki67) and p53 protein expression. Cytometric image analysis for nuclear DNA content was also performed. K-ras mutations were investigated by DNA sequence analysis.
Neoplastic, predominantly spindle-shaped cells and osteoclast-like giant cells were positive for mesenchymal markers CD68, LCA, and A1ACT. These spindle-shaped cells were also positive for human muscle actin. Spindle-shaped cells of seven tumors were also positive for epithelial markers carcinoembryonic antigen, epithelial membrane antigen, or keratin. Nine tumors contained a variable number of pleomorphic giant cells in addition to osteoclast-like giant cells. Pleomorphic giant cells were much less positive for mesenchymal markers than were osteoclast-like giant cells, but they were positive for some epithelial markers. A high percentage of spindle-shaped and pleomorphic giant cells were positive for Ki67. Diploid and aneuploid populations were present in varying proportions in both spindle cells and pleomorphic giant cells. The nuclei of osteoclast-like giant cells, however, were diploid and not proliferating. Spindle-shaped and pleomorphic giant cells were positive for p53 protein in 5 of 10 cases. Five of six tumors studied were positive for K-ras mutations.
The distinction between tumors with osteoclast-like giant cells and undifferentiated carcinomas with pleomorphic giant cells is often not clear-cut. Both types of tumors have mesenchymal and epithelial characteristics in varying proportions and may arise from an undifferentiated pancreatic stem cell. Long-term survival of two patients suggests that some tumors with osteoclast-like giant cells may have a better prognosis than the usual pancreatic ductal adenocarcinoma.
伴有破骨细胞样巨细胞的胰腺肿瘤组织发生及侵袭性尚不明确。其与伴有多形性巨细胞的胰腺未分化（间变性）癌之间的关系（若存在）也不清楚。
采用免疫组织化学方法研究11例伴有破骨细胞样巨细胞的肿瘤，检测上皮和间充质标志物、增殖标志物（Ki67）及p53蛋白表达。还进行了细胞核DNA含量的细胞图像分析。通过DNA序列分析研究K-ras基因突变情况。
肿瘤性、主要为梭形的细胞及破骨细胞样巨细胞对间充质标志物CD68、LCA和A1ACT呈阳性。这些梭形细胞对人肌动蛋白也呈阳性。7例肿瘤的梭形细胞对上皮标志物癌胚抗原、上皮膜抗原或角蛋白也呈阳性。9例肿瘤除破骨细胞样巨细胞外还含有数量不等的多形性巨细胞。多形性巨细胞对间充质标志物的阳性程度远低于破骨细胞样巨细胞，但对某些上皮标志物呈阳性。高比例的梭形和多形性巨细胞对Ki67呈阳性。二倍体和非整倍体群体在梭形细胞和多形性巨细胞中均以不同比例存在。然而破骨细胞样巨细胞的细胞核为二倍体且不增殖。10例中有5例的梭形和多形性巨细胞对p53蛋白呈阳性。所研究的6例肿瘤中有5例K-ras基因突变呈阳性。
伴有破骨细胞样巨细胞的肿瘤与伴有多形性巨细胞的未分化癌之间的区分往往不明确。这两种类型的肿瘤均有不同比例的间充质和上皮特征，可能起源于未分化的胰腺干细胞。两名患者的长期存活提示一些伴有破骨细胞样巨细胞的肿瘤预后可能优于普通胰腺导管腺癌。
